While substantial progress have been made in the global HIV response, impact have been uneven. Uganda provides a prime case study. Uganda was an early epicenter of the epidemic, with the first report of ?slim disease? in East Africa published by our group in 1985. Over the next two decades, Uganda was a leader in efforts to control the epidemic. More recently, new HIV infections remain substantial, particularly in hard-to- reach subpopulations, and the modern Ugandan response to the HIV epidemic presents an improving but mixed picture. Despite moderate scale-up of HIV services, it is estimated that there are still approximately 28,000 yearly AIDS-related deaths and 83,000 new infections in the setting of suboptimal antiretroviral therapy and male circumcision coverage. High mobility, suboptimal linkage and retention in care, persistent high risky sexual behaviors, and an incomplete understanding of HIV transmission dynamics continue to compromise an optimal response. Adding to these challenges are the increasing identification of HIV ?hotspots? in Uganda, geographic areas of high HIV burden, where HIV services are often limited. Uganda, like most PEPFAR countries, has adopted more aggressive approaches, including Test and Treat All and introducing Pre- Exposure Prophylaxis (PrEP). However, the impact of these approaches is unclear and will need close monitoring to understand their implementation and impact. This complexities of HIV transmission dynamics and responses raise many critical research questions which impact both Ugandan and Sub-Saharan African policies and programs. In order to address these research areas, it is essential that local capacity be strengthened. In particular, we believe capacity must be built in a multidisciplinary fashion to better understand and reduce HIV incidence in Uganda and beyond, a high priority NIH research area. Our group has a long and successful legacy of training leaders in HIV research and are strongly positioned to build upon this foundation. We propose a multidisciplinary approach to developing scientific capacity in Uganda which will emphasize 3 synergistic areas: (1) Implementation Science, (2) Geospatial Analysis/Infectious Disease Dynamics and (3) Virology/Immunology/HIV Cure. These disciplines span the clinic, community, modeling, and the lab sciences and will ensure that we reach the long-term goals and objectives of the program, which are that Ugandan institutions will have the research capacity needed to understand, respond to, and eventually control the HIV epidemic. We will involve 22 trainees in multidisciplinary bachelor, master's, PhD, and post- graduate level training, mostly in Uganda. The primary beneficiaries of this training will be the Rakai Health Sciences Program and the Makerere University School of Public Health in Uganda with whom Johns Hopkins University, the applicant institution, has had a highly successful collaborative relationship for 30 years. Our anticipated outcome is to have developed a world-class cadre of Ugandan research capacity capable of leading Uganda to the end of its HIV epidemic.